Best of 2011

Progress in Cord Blood Transplants

The number of patients who can receive lifesaving cord blood transplants may soon dramatically increase thanks to Dr. Colleen Delaney’s research

Cord blood donors don’t have to genetically match the patients getting transplants, making cord blood an intriguing alternative to bone marrow. The problem is that cord blood units contain relatively few stem cells. This means it takes longer for white blood cells to recover in transplant patients, leaving them vulnerable to infection.

In 2011, Delaney continued pioneering a way to increase the number of stem cells in cord blood units. In clinical trials, her team is using these expanded units to significantly accelerate white blood cell recovery in patients with leukemia and other blood cancers. And the research that sparked this breakthrough has led Delaney to develop new cord blood treatments that extend far beyond stem cell transplant.

"We’re making progress on a new therapy that could potentially help almost anyone with a low white blood cell count, whether it’s a chemotherapy patient or someone who survived a nuclear explosion," Delaney says.

Getting stem cells to divide, but not mature

Delaney’s team spearheaded a technique that increases the number of stem cells in a cord blood unit by 150 times or more. Her work builds on a breakthrough by her mentor, Dr. Irwin Bernstein, who figured out how to instruct blood stem cells to multiply by activating a pathway within those cells. Delaney and Bernstein are Seattle Children’s physicians who performed this research at Fred Hutchinson Cancer Research Center (FHCRC). Clinical trials for Delaney’s work are being conducted at the FHCRC-Seattle Cancer Care Alliance and at Seattle Children’s Hospital.

"Other researchers expanded these stem cells but couldn’t stop them from maturing. Only immature cells can differentiate into any cell type once they’re transplanted," Delaney says. "We applied Dr. Bernstein’s discoveries to cord blood stem cells in a way that got them to divide without maturing."

Recent advances move clinical trials forward

In 2010, Delaney and her colleagues published a landmark paper in Nature Medicine, a leading journal on biomedical research, detailing how patients receiving expanded cord blood units engrafted much faster than those receiving non-expanded units in a phase I clinical trial.

Delaney’s work took another important step in 2011, when her team proved that cells expanded in Seattle could be effective when shipped to out-of-state hospitals and given to patients there. Now Delaney is preparing to conduct nationwide phase II trials. She expects these trials to take four to five years to complete, plus another year of data analysis.

"If these expanded units continue to be effective, the therapy could move forward to FDA approval and more widespread use," she says.

Applications beyond transplants

Delaney is also looking at whether infusions of expanded cord blood could help patients with low white blood cell count by boosting their bodies’ capacity to fight infections. This could be done without genetic matching because the expanded cell products do not have T cells to trigger immune reactions in patients.

"In theory, infusing a patient with expanded units could reduce the risk of infection in anyone, regardless of their race, ethnicity or tissue typing," says Delaney, who is leading clinical trials to see if the infusions limit infections in patients undergoing chemotherapy.

The trials could ultimately lead to a variety of other applications. Delaney has even received federal funding to determine whether expanded cord blood cells could help populations recover from a nuclear attack or accidental radiation exposure.

"If there was a nuclear explosion, the radiation levels would be similar to what bone marrow transplant patients receive," Delaney says. "We could potentially rescue victims with stem cells."

A personal mission

Delaney’s success is particularly striking because she never meant to spend her career in the lab. Her goal was to focus on clinical pediatric oncology. During a fellowship in Bernstein’s lab, she was won over by the opportunity to advance lifesaving cord blood therapies.

Eleven years later, she is still driven by a passion for bedside care—a passion reflected in the snapshots of her clinical trial participants she hangs alongside pictures of her children in her office.

"Those patients will be imprinted on me for the rest of my life," Delaney says.

"Other researchers expanded these stem cells but couldn’t stop them from maturing. Only immature cells can differentiate into any cell type once they’re transplanted. We applied Dr. Bernstein’s discoveries to cord blood stem cells in a way that got them to divide without maturing." ~ Dr. Colleen Delaney

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